Comparable efficacy and safety of taletrectinib for advanced ROS1+ non–small cell lung cancer across pivotal studies and between races and world regions.

Abstract

8643 Background: Taletrectinib is a highly potent, next-generation, central nervous system–active, selective ROS1 tyrosine kinase inhibitor (TKI) that was evaluated in 2 pivotal ROS1+ non–small cell lung cancer (NSCLC) phase 2 trials: the regional TRUST-I (NCT04395677) and global TRUST-II (NCT04919811) studies. While earlier trials suggest its safety and efficacy data are consistent across racial and geographic factors, further analysis is required to confirm the consistency of outcomes and applicability of results across regions. Here, we compare the efficacy and safety of taletrectinib within and between the pivotal regional TRUST-I and global TRUST-II studies through predefined subgroup analyses. Methods: The pivotal cohorts of TRUST-I (N=173) and TRUST-II (N=159) had similar study designs, which included the same primary endpoint (confirmed objective response rate [cORR] by independent review committee per RECIST v1.1) and secondary endpoints, as well as similar inclusion/exclusion criteria and safety evaluation methods. Key efficacy and safety profiles were compared in 3 ways: (a) between TRUST-I and TRUST-II, (b) across Western (North America and Europe) and Asian regions, and racial subgroups, in the pooled study population of TRUST-I and TRUST-II, and (c) between Western and Asian regions and other subgroups in the global TRUST-II study. Relative risk (RR) and associated 95% confidence intervals (CIs) via the Wald method were used to compare data (data cutoff June 2024). Results: When comparing TRUST-I and TRUST-II, cORRs were consistent for TKI-naive (91% vs 85%; RR: 0.94 [95% CI: 0.83, 1.07]) and TKI-pretreated pts (52% vs 62%; RR: 1.20 [95% CI: 0.87, 1.66]). Rates of grade ≥3 treatment-emergent adverse events (TEAEs) were consistent across both studies (51% vs 51%, RR: 1.0 [95% CI: 0.81, 1.24]). TEAEs leading to dose interruptions (41% vs 40%) and discontinuations (6% vs 8%) were similar. In subgroup analyses of the pooled patient population by race, Asian and non-Asian patients had similar cORRs in both TKI-naive (89% vs 84%; RR: 0.94 [95% CI: 0.77, 1.15]) and TKI-pretreated (52% vs 68%; RR: 1.30 [95% CI: 0.93, 1.82]) groups. Comparison of different efficacy and safety profiles among subgroups in the pooled data set also showed consistency among races and regions. Within the multiregional TRUST-II study, cORRs were high in TKI-naive patients regardless of region (Western: 81%; Asia: 88%), prior chemotherapy (yes: 90%; no: 84%), and race (White: 83%; Asian: 86%; other: 86%). Similarly, major safety profiles were comparable between Asian and Western patients and between races within TRUST-II. Conclusions: Taletrectinib showed comparable efficacy and safety that were not impacted by geographic and racial factors. Therefore, the clinical benefit of taletrectinib is broadly applicable to ROS1+ NSCLC patients globally. Clinical trial information: NCT04395677 , NCT04919811 .